Ankylosing spondylitis Dr Chris Edwards

Ankylosing spondylitis
Dr Chris Edwards
Prevalence
• Worldwide prevalence up to 0.9%1
• Prevalence varies by population and is closely
correlated to prevalence of HLA-B272
• Prevalence also varies among ethnic groups
• Male:Female – 5:1
g of onset: 15 – 35 yyears
• Peak age
1. Braun et al. Arthritis Rheum 1998; 41: 58-67. 2. Sieper J et al. Ann Rheum Dis 2002; 61
(Suppl. III): iii8-18.
Co-morbidity & co-mortality
• There may also be extra-articular manifestations of AS.
• Spinal fracture - most serious complication encountered
i AS
in
• Prostatitis is prevalent among men with AS
• Long-term
L
t
disease
di
iincreases risk
i k off cardiovascular
di
l
complications
• Acute anterior uveitis occurs in 20% to 40% of cases
cases.
Other extra-articular manifestations include aortic
regurgitation, pulmonary fibrosis, and, among male
patients, prostatitis
Sieper J et al. Ann Rheum Dis 2002; 61 (Suppl. III): iii8-18.
Disease burden – cost impact
• Etanercept provides a rapid reduction in:
• disease activity
• Objective functional measures
• Work instability
This suggests that therapy may be cost effective in
terms of work disability
Barkham N et al Ann Rheum Dis 2008; 67 (suppl II) : 382
Productivity Costs of ankylosing spondylitis in
the USA, The Netherlands, France and Belgium
USA ((n=241)
241)
Netherlands
N
th l d
(n=130)
F
France
(n=
( 53)
B l i
Belgium
((n= 26)
Work disability
(%)
12
41*
23*
9*
Days sick leave
pt/y; † mean
(range)
Not stated
19 (0–130)
6 (0–77)
9 (0–60)
Friction
costs/pt/y: †
mean (range)
(
)
Not applied
€1257 (0–7356)
€428 (0–5979)
€476 (0–2354)
Human capital
costs/pt/y;
mean (range)
(
)
US $4945
(0–45800)
€4227
(0–39145)‡
€8862
(0–46818)
€3188
(0–43550)
€3609 (0–
34320)
*Adjusted for age and sex. Includes patients with partial work disability who continue in a part-time paid job in The
Netherlands and France † in those with a paid job ‡ converted to Euros using 1998 purchasing power parities
Sieper J et al. Ann Rheum Dis 2002; 61 (Suppl. III): iii8-18.
Disease burden – quality of life impact
Understanding the burden of disease
Quality of Life
An individuals’ perception of their position in the
context of the culture and value systems in which
th lilive and
they
d iin relation
l ti tto th
their
i
goals, expectations, standards and concerns
World Health Organisation (1995)
Quality of Life
•
Ph i l ffunction
Physical
i
•
Employment, household
management
ADL, mobility, physical activity
•
Symptoms
Pain, sleep, stiffness, fatigue
•
•
Global health
•
Emotional well-being
Anxiety,
y control, self-esteem
•
Cognitive function
Cognition, concentration
Cognition
concentration,
memory
Social well-being
Relationships, opportunities,
sexual activity and satisfaction
R l activities
Role
ti iti
•
Personal constructs
Life satisfaction, stigma,
Bodily appearance, spirituality
Work disability: AS-specific
AS specific
• Employment
E l
t rates
t range 55–85%
55 85%
• 50% of studies report < 70%
• Work disability rates range 3–41%
• 50% of studies report
p > 20%
• Risk factors:
•
•
•
•
•
•
Age
Disease duration
Physical function**
Pain
Physically demanding jobs
Lower education level
Sieper et al, 2002; Boonen et al, 2001
Work disability: AS-specific
AS specific
• Workforce withdrawal
•
•
•
•
•
1st year
5 years
10 years
15 years
20 years
5%
13%
21%
23%
31%
• 3.1x higher
g
than g
general p
population
p
Sieper et al, 2002; Boonen et al, 2001
Social well
well-being
being
•
Old studies
Older
di suggest ffew problems
bl
•
Intimate relationships
• Men no problems; women less enjoyment
• Few report marital strain / avoidance
• 27% mild discomfort; 7% severe discomfort
•
(Elst et al, 1984)
(Dalyan et al, 1999)
(Wordsworth et al, 1986)
Impact on daily life (n 129) - % reporting limitations:
•
•
•
•
1% social interactions
2% communication
3% normal role activities
6% leisure activities
(Bakker et al, 1995)
Social well
well-being:
being: AS and RA
• Health status comparison: SF-36 generic health status
• AS better Physical health
• RA better Mental health
• No g
group
p differences for:
• SF-36: Pain, Physical or Emotional-Role functioning,
Social Function, Vitality or General Health
• Fatigue (MFI) or Behavioural Coping (CORS)
• Work: +ve association with physical health in both groups
Chorus et al, 2003
SF-36 scores for patients with RA and
patients with AS
100
80
RA male
60
AS
S male
ae
40
RA female
20
AS female
0
Physical Component
Summary
Chorus et al, 2003
Mental Component
Summary
Immunology and pathogenesis
Pathogenesis
• Immune-mediated, involving:
•
•
•
•
HLA-B27
Inflammatory cellular infiltrates
Cytokines such as TNFα and IL-10
Genetic and environmental factors
Sieper J et al. Ann Rheum Dis 2002; 61 (Suppl. III): iii8-18.
Diagnosis
AS/SpA: Characteristic Parameters
Used for Early Diagnosis
Symptoms
IInflammatory
fl
t
Back Pain
Imaging
Lab
Patient’s
history
y
HLA-B27
Good response
to NSAIDs
Rudwaleit M, et al. Ann Rheum Dis. 2004;63:535-43
ESR/CRP
Family history
AS/Axial SpA:
Typical Manifestations/Features
Sensitivity
Specificity
LR+
LR-
Inflammatory back pain
75%
76%
3.1
0.33
Enthesitis ((heel p
pain))
37%
89%
3.4
Peripheral arthritis
40%
90%
4.0
Dactylitis
18%
96%
4.5
Anterior uveitis
22%
97%
73
7.3
Positive family history for SpA
32%
95%
6.4
Psoriasis
10%
97%
3.3
Inflammatory bowel disease
4%
99%
4.0
Good response to NSAIDs
77%
85%
5.1
Elevated acute phase
reactants
50%
80%
2.5
Positive
likelihood ratio
HLA-B27
(axial involvement)
0.29
0.27
(LR+)
90% = sensitivity/(100-specificity)
90%
9.0
0.11
Negative likelihood ratio (LR-)
= (100-sensitivity/specificity)
MRI ((STIR))
90%
90%
9.0
0.11
Rudwaleit M, et al. Ann Rheum Dis. 2004;63:535-43
Rudwaleit M, Feldtkeller E. and Sieper J. Ann Rheum Dis 2007;. In press.
Spondyloarthritis - main manifestations
1. Axial involvement/spinal inflammation
1
2. Peripheral arthritis
3 Peripheral enthesitis
3.
SpA subtypes
1.
Ankylosing spondylitis (AS)
2.
Undifferentiated SpA
3.
Psoriatic SpA
p
4.
Reactive SpA
5
5.
SpA
S
A associated
i t d with
ith chronic
h
i
inflammatory bowel diseases
Axial SpA
AS
Ankylosing Spondylitis: a chronic inflammatory
rheumatic
h
ti disease
di
with
ith debilitating
d bilit ti potential
t ti l
24 years
•
main
i affection
ff i
off the
h spine,
i
entheses,
h
peripheral joints and the eye
•
main symptom: inflammatory back
pain
AS
49 years
•
1/3 of patients with severe disease
•
overall prevalence high (0.5%)
•
etiology unknown
•
definite genetic load (new genes !)
•
strong HLA B27 association
•
l t diagnosis
late
di
i (5-7
(5 7 years))
•
reduced quality of life
•
increased risk of unemployment
•
direct/indirect costs
Zink A et al, J Rheum 2000, 2001; Boonen A et al., Ann Rheum Dis 2001, 2002, Ward M et al. J Rheum 2001, A&R 2002
Possible Outcomes of Ankylosing Spondylitis
Age at Onset of Symptoms and
Age at Diagnosis in AS (DVMB)
Time from first symptoms to diagnosis: 5–10
5 10 yrs
100
Age at onset of
symptoms
Pa
atients (%
%)
80
Age at diagnosis
60
40
n=1396
20
0
920 males
476 females
Age (yrs)
0
10
20
Feldtkeller E, et al. Z Rheumatol. 1999;58:21-30.
Feldtkeller E, et al. Rheumatol Int. 2003;23:61-6.
30
40
50
60
70
Differentiating clinical features of IBP in
patients
ti t < 45 years with
ith chronic
h
i back
b k pain
i
( > 3 months )
• Morning stiffness > 30 min
• Improvement with exercise,
* not with rest
* 2. half of the night because of pain
• Awakening at
• Alternating buttock pain
*
*
Diagnosis of IBP if 2 / 4 criteria are fulfilled
sensitivity
iti it
specificity
70 %
81 %
(AS n = 101; non-AS back pain n = 112)
Rudwaleit M et al. A&R 2006
Use of the new IBP criteria as diagnostic
criteria
it i iin individual
i di id l patients
ti t
• Morning stifness > 30 min
• Improvement
p
by
y movement,, but not rest
• Wakening up in the 2nd half of the night because of pain
• Alternating buttock pain
≥ 2 out of 4 positive
≥ 3 out of 4 positive
Sensitivity 70.3%
Sensitivity 33.6%
Specificityy 81.2%
Specificityy 97.3%
LR+ 3.7
LR+ 12.4
Rudwaleit et al. Arthritis Rheum 2006;54:678-81
X-ray evidence of sacroiliitis: a prerequisite for
di
diagnosing
i AS (modified
( difi d NY criteria
it i 1984)
van der Linden Arthritis Rheum 1984
A role for magnetic resonance imaging in the
diagnosis of early sacroiliitis in
pondyloarthritides
T1
T2
A ti sacroiliac
Active
ili inflammation
i fl
ti
Braun J et al. A&R 1994
The diagnostic value of scintigraphy in
assessing sacroiliitis in AS - a systematic
literature research
•
Outt off a total
O
t t l off 99 articles
ti l about
b t scintigraphy
i ti
h ffound,
d 25 were
included into the analysis.
•
y for scintigraphy
g p y to detect sacroiliitis was 52 % for
Overall sensitivity
patients with established AS (N= 361) and 49 % for patients with
probable sacroiliitis (N= 255).
•
Sensitivity of scintigraphy in AS patients with inflammatory back pain
(indicating ongoing inflammation) was 53 % (N= 112) and in patients
with AS and suspected sacroiliitis with magnetic resonance imaging
showing acute sacroiliitis (as a gold standard) was 53 % (N=62).
(N 62).
•
In controls with MLBP specificity was 78 % (N= 60), resulting in LRs
not higher than 2.5-3.0.
•
The data suggest that scintigraphy of the sacroiliac joints is at the
most of limited diagnostic value for the diagnosis of established AS
including the early diagnosis of probable / suspected sacroiliitis.
Song I et al. Ann Rheum Dis. 2008 Jan 29 [Epub ahead of print]
Early back pain cohort: clinical items vs.
i
imaging
i for
f the
th diagnosis
di
i off spondyloarthritis
d l
th iti
84
90
n = 69 with IBP < 2 years
80
70
60
X-rays
X
rays
MRI
ESSG criteria
50
33
40
30
21
20
10
0
X
X-rays
MRI
ESSG
criteria
Heuft-Dorenbosch L et al. Ann Rheum Dis. 2006 Jun;65(6):804-8. Epub 2005 Oct 11
What is helpful for an early diagnosis of
AS ?
• Screen young patients ( < 45 y) with back pain >
3 months
• Ask for inflammatory back pain
• Ask for other signs of spondyloarthritis (uveitis,
enthesitis)
• Do the HLA B27 test
• Add imaging when necessary (MRI, X-rays)
AS assessment tools
AS Measures of Disease Outcome
• Bath
B th A
Ankylosing
k l i S
Spondylitis
d liti (BAS) scales
l
•
•
•
•
BASDAI – Disease Activity Index
BASFI – Functional
F
ti
l Index
I d
BASGI – Global Index
BASMI – Metrology Index
• BASRI – Radiographic Index
• Other measurement indexes
• SF-36 – 36-Item Medical Outcomes Study Short-Form
Health Survey
• ASAS – Assessments in Ankylosing Spondylitis
Working Group Improvement Criteria
Disease Activity Assessment
Index
Metric
BASFI
Di bilit L
Disability
Levell
BASDAI
Disease Activity
y Level
BASMI
Spinal Mobility
ASAS - IC
Composite Sum of Disease Activity
BASFI = Bath Ankylosing Spondylitis Functional Index
BASDAI = Bath Ankylosing Spondylitis Disease Activity Index
BASMI = Bath Ankylosing Spondylitis Metrology Index
ASAS - IC = ASsessment in Ankylosing Spondylitis Improvement Criteria
Bath Ankylosing Spondylitis Functional
Index (BASFI)
•
Vi
Visual
l analogue
l
scale
l
•
•
Easy (1) – impossible (10)
Mean (VAS) of 10 questions:
1.
1
2.
3.
4.
5.
5
6.
7.
8.
9.
10
10.
Putting on your socks or tights without help or aids
Bending forward from the waist to pick up a pen from the floor
without an aid
Reaching up to a high shelf without help or aids (e.g helping
hand)
Getting up out of an armless dining room chair without using
your hands or other help
Getting up off the floor without help from lying on your back
Standing unsupported for ten minutes without discomfort?
Climbing 12-15 steps without using a handrail or walking aid
(one foot on each step)?
Looking over your shoulder without turning your body?
Doing physically demanding activities (eg physio exercises,
gardening, sport)?
Doing a full day
day’s
s activities at home or at work?
relate to the
functional
anatomy of
subjects
relate to a
subject’s
ability to cope
with everyday
life
Calin, J Rheumatol 1994;21:2281-85.
Bath Ankylosing Spondylitis Disease
Activity Index (BASDAI)
Visual analogue scale (0 – 10 cm)
•
None (1) – Very severe (10)
1. Fatigue - How would you describe the overall level of fatigue/tiredness you
have experienced?
p
2. Spinal pain - How would you describe the overall level of AS neck, back or hip
pain you have had?
3. Joint pain - How would you describe the overall level of pain/swelling in joints
other than neck, back or hips you have had?
4. Enthesitis - How would you describe the overall level of discomfort you have
had from any areas tender to touch or pressure?
5. Inflammation:
1. Duration morning stiffness - How would you describe the overall level of
morning stiffness you have had from the time you wake up?
2 Severity
2.
S
it morning
i stiffness
tiff
- How
H
llong d
does your morning
i stiffness
tiff
llastt
from the time you wake up? (scale of 0 to >2 hrs)
BASDAI =
0 2 [F + S + J + E + 0.5
0.2
0 5 (Duration + Severity Morning Stiffness)]
•
Range 0 – 10
Garrett, J Rheumatol 1994;21:2286-91.
Bath Ankylosing Spondylitis Metrology
Index (BASMI)
•
Represented
R
d as aggregate score (ranging
(
i
from
f
0 to 10) using
i
the variables below
Score
Measurement
0
1
2
Tragus-to-wall
< 15 cm
15 to 30 cm
>30 cm
Lumbar flexion (modified
Schober test)
> 4 cm
2 to 4 cm
< 4 cm
> 70º
20 to 70º
< 20º
Lumbar side flexion
> 10 cm
5 to 10 cm
< 5 cm
Intermalleolar distance
> 100 cm
70 to 100 cm
< 70 cm
Cervical rotation
Jenkinson, J Rheumatol 1994;21:1694-98.
Objectives of disease management
•
R d
Reduce
and/or
d/ prevent deleterious
d l
i
effects
ff
of:
f
• Inflammation
• Ankylosis
y
• Abnormal posture
•
Aim for:
•
•
•
•
•
•
No or llow di
N
disease activity
ti it ((pain,
i stiffness,
tiff
MRI,
MRI CRP)
Good function, no disability
No structural damage
g ((no g
growth of syndesmophytes)
y
y )
Good quality of life
No increased cardiovascular morbidity
Normal life expectancy
Dougados M et al. J.Rheumatol 2001;28-62:16-20